9n3m

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'''Unreleased structure'''
 
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The entry 9n3m is ON HOLD until Paper Publication
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==SARS-CoV-2 Mpro L50F/E166A/L167F triple mutant bound to inhibitor==
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<StructureSection load='9n3m' size='340' side='right'caption='[[9n3m]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
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Authors: Lu, J., Chen, P., Demmon, S., Fischer, C., Vederas, J.C., Lemieux, M.J.
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== Structural highlights ==
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<table><tr><td colspan='2'>[[9n3m]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Severe_acute_respiratory_syndrome_coronavirus_2 Severe acute respiratory syndrome coronavirus 2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9N3M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9N3M FirstGlance]. <br>
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Description: SARS-CoV-2 Mpro L50F/E166A/L167F triple mutant bound to inhibitor
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9&#8491;</td></tr>
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[[Category: Unreleased Structures]]
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1BVV:(1S,2S,4S)-2-{[3-cyclopropyl-N-(4-methoxy-1H-indole-2-carbonyl)-L-alanyl]amino}-1-hydroxy-4-methyl-5-(methylamino)-5-oxopentane-1-sulfonic+acid'>A1BVV</scene></td></tr>
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[[Category: Demmon, S]]
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=9n3m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9n3m OCA], [https://pdbe.org/9n3m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9n3m RCSB], [https://www.ebi.ac.uk/pdbsum/9n3m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9n3m ProSAT]</span></td></tr>
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[[Category: Fischer, C]]
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</table>
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[[Category: Vederas, J.C]]
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== Function ==
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[[Category: Lu, J]]
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[https://www.uniprot.org/uniprot/R1A_SARS2 R1A_SARS2] Multifunctional protein involved in the transcription and replication of viral RNAs. Contains the proteinases responsible for the cleavages of the polyprotein.[UniProtKB:P0C6X7] Inhibits host translation by interacting with the 40S ribosomal subunit. The nsp1-40S ribosome complex further induces an endonucleolytic cleavage near the 5'UTR of host mRNAs, targeting them for degradation. Viral mRNAs are not susceptible to nsp1-mediated endonucleolytic RNA cleavage thanks to the presence of a 5'-end leader sequence and are therefore protected from degradation. By suppressing host gene expression, nsp1 facilitates efficient viral gene expression in infected cells and evasion from host immune response.[UniProtKB:P0C6X7] May play a role in the modulation of host cell survival signaling pathway by interacting with host PHB and PHB2. Indeed, these two proteins play a role in maintaining the functional integrity of the mitochondria and protecting cells from various stresses.[UniProtKB:P0C6X7] Responsible for the cleavages located at the N-terminus of the replicase polyprotein. In addition, PL-PRO possesses a deubiquitinating/deISGylating activity and processes both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains from cellular substrates. Participates together with nsp4 in the assembly of virally-induced cytoplasmic double-membrane vesicles necessary for viral replication. Antagonizes innate immune induction of type I interferon by blocking the phosphorylation, dimerization and subsequent nuclear translocation of host IRF3. Prevents also host NF-kappa-B signaling.[UniProtKB:P0C6X7] Participates in the assembly of virally-induced cytoplasmic double-membrane vesicles necessary for viral replication.[UniProtKB:P0C6X7] Cleaves the C-terminus of replicase polyprotein at 11 sites. Recognizes substrates containing the core sequence [ILMVF]-Q-|-[SGACN]. Also able to bind an ADP-ribose-1''-phosphate (ADRP).[UniProtKB:P0C6X7] Plays a role in the initial induction of autophagosomes from host reticulum endoplasmic. Later, limits the expansion of these phagosomes that are no longer able to deliver viral components to lysosomes.[UniProtKB:P0C6X7] Forms a hexadecamer with nsp8 (8 subunits of each) that may participate in viral replication by acting as a primase. Alternatively, may synthesize substantially longer products than oligonucleotide primers.[UniProtKB:P0C6X7] Forms a hexadecamer with nsp7 (8 subunits of each) that may participate in viral replication by acting as a primase. Alternatively, may synthesize substantially longer products than oligonucleotide primers.[UniProtKB:P0C6X7] May participate in viral replication by acting as a ssRNA-binding protein.[UniProtKB:P0C6X7] Plays a pivotal role in viral transcription by stimulating both nsp14 3'-5' exoribonuclease and nsp16 2'-O-methyltransferase activities. Therefore plays an essential role in viral mRNAs cap methylation.[UniProtKB:P0C6X7]
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[[Category: Lemieux, M.J]]
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__TOC__
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[[Category: Chen, P]]
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</StructureSection>
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[[Category: Large Structures]]
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[[Category: Severe acute respiratory syndrome coronavirus 2]]
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[[Category: Chen P]]
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[[Category: Demmon S]]
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[[Category: Fischer C]]
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[[Category: Lemieux MJ]]
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[[Category: Lu J]]
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[[Category: Vederas JC]]

Revision as of 06:21, 20 August 2025

SARS-CoV-2 Mpro L50F/E166A/L167F triple mutant bound to inhibitor

PDB ID 9n3m

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